The purpose of this a multi-center, open-label, phase II roll-over protocol is to evaluate safety, as measured by hematology, urinalysis, clinical chemistry, and adverse experience monitoring, of T-20 given by intermittent subcutaneous injection (SQI) to HIV-1 positive adults for 48 weeks. The secondary objectives are to determine plasma pharmacokinetics; antiviral activity, as measured by changes in plasma HIV-1 RNA levels; and, immunological effect, as measured by changes on CD4+ cell counts. Despite the antiviral efficacy associated with protease inhibitor-containing regimens, approximately 20%-50% of the subject population will exhibit a rebound in HIV-1 RNA levels within 52 weeks of initiating therapy. In addition, the treatment of antiretroviral experienced subjects has been less successful than the treatment of subjects who are naive to antiretroviral therapy. The six-month success rate of salvage regimens for PI failures has varied from 10%-60. Failure of salvage regimens is at least partially due to broad intra-class cross-resistance, which exists among RTIs and Pls. The investigational agent, T-20, is a 36-amino acid synthetic peptide composed of naturally occurring L-amino acid residues. The primary sequence of T-20 was derived from a naturally occurring motif (amino acid residues 643-678) within the gp4l transmembrane glycoprotein of HIV-1 LAI. The results of non-clinical mechanism of action studies indicate that T-20 exhibits potent and selective inhibition of de novo infection and cell to cell virus transmission by binding to a critical region of gp4l which regulates the fusion of virus to host cell membranes. Results of a Phase I/II clinical trial indicate that T-20 was safe at all dose levels evaluated and exhibited potent antiretroviral activity when given 100 mg intravenously or subcutaneously on a BID schedule for 14 to 28 days. Eligible subjects who qualify for participation will receive T-20 SQI every 12 hour at 50 mg in combination with two or more new or recycled antiretrovirals specific to the individual. The individualized antiretroviral regimen will be determined by subject's antiretroviral history and a genotype analysis performed at the screening visit. The total study participation will be 53 weeks, including a 21 screening period, a 48-week-treatment period, and a 2-week follow-up period. Approximately 93 HIV-infected adults will be enrolled at 12 centers. Prior exposure to T-20 is required (i.e., in Protocols TRI-001 or TRI-003). There are no limitations on prior antiretroviral exposure. Efficacy endpoints include: CD4 and HIV RNA change from baseline, % subjects achieving HIV RNA below limit of quantification, T-20 plasma concentration at selected intervals including a 12 hour outpatient plasma pharmacokinetic profile of T-20 on Day 28.